Quantitative structure-activity relationship of phenoxyphenyl-methanamine compounds with 5HT2A, SERT, and hERG activities.
QSAR models have been used to evaluate activities for compounds in the phenoxyphenyl-methanamine (PPMA) class of compounds. These models utilize Hammett-type donating-withdrawing substituent values as well as simple parameters to describe substituent size and elucidate the SAR of the 'A' and 'B' rings. Using this methodology, intuitive QSAR relationships were found for the three biological activities with R(2) values of 0.73, 0.45, and 0.58 for 5HT(2A), SerT, and hERG activities.
Mente
Scot
S
Pfizer Global Research and Development, Groton Laboratories, 1 Eastern Point Road, Groton, CT 06355, USA. scot.mente@pfizer.com
Gallaschun
Randall
R
Schmidt
Anne
A
Lebel
Lorrie
L
Vanase-Frawley
Michelle
M
Fliri
Anton
A
D020650:Combinatorial Chemistry Techniques; D003863:Depression / Q000188:drug therapy; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D008744:Methylamines / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011985:Receptors, Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D051638:Ether-A-Go-Go Potassium Channels; D008744:Methylamines; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C078730:serotonin 5 receptor; C027451:methylamine